| Autor: |
Medrano-Garcia S; Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), 61231 Bad Nauheim, Germany.; Institute for Lung Health (ILH), Justus Liebig University, 35305 Giessen, Germany.; Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine and Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28040 Madrid, Spain., Morales-Cano D; Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, 28040 Madrid, Spain.; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28040 Madrid, Spain., Barreira B; Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, 28040 Madrid, Spain., Vera-Zambrano A; Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, 28040 Madrid, Spain., Kumar R; Department of Medicine, University of California, San Francisco, CA 94143, USA., Kosanovic D; Department of Pulmonology, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia., Schermuly RT; Department of internal Medicine, Justus-Liebig University, Member of the German Center for Lung Research (DZL), 35305 Giessen, Germany., Graham BB; Department of Medicine, University of California, San Francisco, CA 94143, USA., Perez-Vizcaino F; Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, 28040 Madrid, Spain., Mathie A; Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham ME4 4BF, UK., Savai R; Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), 61231 Bad Nauheim, Germany.; Institute for Lung Health (ILH), Justus Liebig University, 35305 Giessen, Germany.; Department of internal Medicine, Justus-Liebig University, Member of the German Center for Lung Research (DZL), 35305 Giessen, Germany., Pullamseti S; Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), 61231 Bad Nauheim, Germany.; Institute for Lung Health (ILH), Justus Liebig University, 35305 Giessen, Germany.; Department of internal Medicine, Justus-Liebig University, Member of the German Center for Lung Research (DZL), 35305 Giessen, Germany., Butrous G; Medway School of Pharmacy, University of Kent and University of Greenwich, Chatham ME4 4BF, UK., Fernández-Malavé E; Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine and Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), 28040 Madrid, Spain., Cogolludo A; Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense de Madrid and Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red Enfermedades Respiratorias, 28040 Madrid, Spain. |
| Abstrakt: |
HIV and Schistosoma infections have been individually associated with pulmonary vascular disease. Co-infection with these pathogens is very common in tropical areas, with an estimate of six million people co-infected worldwide. However, the effects of HIV and Schistosoma co-exposure on the pulmonary vasculature and its impact on the development of pulmonary vascular disease are largely unknown. Here, we have approached these questions by using a non-infectious animal model based on lung embolization of Schistosoma mansoni eggs in HIV-1 transgenic (HIV) mice. Schistosome-exposed HIV mice but not wild-type (Wt) counterparts showed augmented pulmonary arterial pressure associated with markedly suppressed endothelial-dependent vasodilation, increased endothelial remodeling and vessel obliterations, formation of plexiform-like lesions and a higher degree of perivascular fibrosis. In contrast, medial wall muscularization was similarly increased in both types of mice. Moreover, HIV mice displayed an impaired immune response to parasite eggs in the lung, as suggested by decreased pulmonary leukocyte infiltration, small-sized granulomas, and augmented residual egg burden. Notably, vascular changes in co-exposed mice were associated with increased expression of proinflammatory and profibrotic cytokines, including IFN-γ and IL-17A in CD4 + and γδ T cells and IL-13 in myeloid cells. Collectively, our study shows for the first time that combined pulmonary persistence of HIV proteins and Schistosoma eggs, as it may occur in co-infected people, alters the cytokine landscape and targets the vascular endothelium for aggravated pulmonary vascular pathology. Furthermore, it provides an experimental model for the understanding of pulmonary vascular disease associated with HIV and Schistosoma co-morbidity. |
